Page 182 - 2014 Printable Abstract Book
P. 182
determining the therapeutic window for all three species. This work is currently supported by the Medical
Countermeasures Against Radiological Threats (MCART) Consortium of the National Institute of Allergy
and Infectious Diseases (NIAID, #HHSN272201000046C) and the Biomedical Advanced Research and
Development Authority (BARDA, #IPIAA12OS99609), through the US DoE under Contract #DE-AC02-
05CH11231.
(PS2-79) Pasireotide mitigates total body irradiation-induced hematopoietic injury in mice. Wei Feng;
Lijian Shao; Wenze Wang; Jianhui Chang; Yi Luo; Junru Wang; Martin Hauer-Jensen; and Daohong Zhou,
Division of Radiation Health, Department of Pharmaceutical Sciences, Little Rock, AR
The severity of bone marrow (BM) injury is a critical determinant of survival after total body
radiation (TBI) in nuclear accidents or radiological terrorism scenarios. However, no safe and effective
radioprotectants are currently available to mitigate ionizing radiation (IR)-induced BM injury at the
present. Our previous studies have shown that pasireotide (SOM230), a novel multi-receptor
somatostatin analog, effectively mitigated IR-induced acute radiation syndrome (ARS) and reduced TBI-
induced mortality in mice even when pasireotide administration starts as late as 72 hours after TBI,
primarily via inhibition of pancreatic secretion of various digestive enzymes to reduce IR-induced intestinal
damage. However, the effects of pasireotide on IR-induced damage to the hematopoietic system have
not been well characterized and thus, were examined in the present study because BM failure is the
primary life‐threatening injuries after exposure to a moderate dose of IR. Specifically, we exposed CD2F1
mice to 6.0 Gy TBI (1.14Gy/min) and administered vehicle or pasireotide (1.0 mg/kg) twice per day by s.c
injection starting at 24 h after TBI for 10 days. The effects of pasireotide on TBI-induced alterations in the
hematopoietic system were examined day 15 and day 30 after TBI. Pasireotide treatment ameliorated the
reduction of RBCs induced by TBI but not that of WBCs and platelets in peripheral blood at day 15 post IR.
Furthermore, the recovery of peripheral blood neutrophils and lymphocytes in irradiated mice was greatly
accelerated upon pasireotide treatment at day 30 after irradiation compared to vehicle treated group. As
expected, TBI dramatically reduced the percentages and numbers of hematopoietic stem cells (HSCs) and
suppressed the clonogenic function of hematopoietic progenitor cells (HPCs) in the bone marrow at both
day 15 and 30 post IR. Pasireotide administration significantly attenuated the reduction of bone marrow
HSCs induced by TBI and improved HPC function revealed by colony forming cell (CFC) assays. These
findings suggest that pasireotide may reduce TBI-induced lethality in mice not only by inhibiting IR-
induced intestinal damage but also in part via attenuating IR-induced hematopoietic injury.
(PS2-80) BIO 300 (genistein oral nanosuspension) protects normal lung tissue and radiosensitizes tumor
1
tissue in a mouse xenograft model of non-small cell lung cancer (NSCLC). Stephen L. Brown ; Michael D.
2
2
2
1
Kaytor ; Karen Lapanowski ; Debra McFall ; John L. Zenk ; Ronald J. Zenk ; John C. Dykstra ; and Benjamin
1
2
1
Movsas, Henry Ford Health System, Detroit, MI and Humanetics Corporation, Minneapolis, MN
1
2
Lung cancer affects a quarter million people in the US annually, accounting for more cancer-
related deaths than any other cancer. Radiation-induced damage to normal lung tissue (pneumonitis and
fibrosis) during radiotherapy remains a significant side effect that could alter the course of therapy and/or
the outcome. The aim of the studies was to evaluate BIO 300 for efficacy in; 1) protecting normal lung
tissue from radiation-induced damage and 2) radiosensitizing tumor tissue. We also evaluated the safety
180 | P a g e
Countermeasures Against Radiological Threats (MCART) Consortium of the National Institute of Allergy
and Infectious Diseases (NIAID, #HHSN272201000046C) and the Biomedical Advanced Research and
Development Authority (BARDA, #IPIAA12OS99609), through the US DoE under Contract #DE-AC02-
05CH11231.
(PS2-79) Pasireotide mitigates total body irradiation-induced hematopoietic injury in mice. Wei Feng;
Lijian Shao; Wenze Wang; Jianhui Chang; Yi Luo; Junru Wang; Martin Hauer-Jensen; and Daohong Zhou,
Division of Radiation Health, Department of Pharmaceutical Sciences, Little Rock, AR
The severity of bone marrow (BM) injury is a critical determinant of survival after total body
radiation (TBI) in nuclear accidents or radiological terrorism scenarios. However, no safe and effective
radioprotectants are currently available to mitigate ionizing radiation (IR)-induced BM injury at the
present. Our previous studies have shown that pasireotide (SOM230), a novel multi-receptor
somatostatin analog, effectively mitigated IR-induced acute radiation syndrome (ARS) and reduced TBI-
induced mortality in mice even when pasireotide administration starts as late as 72 hours after TBI,
primarily via inhibition of pancreatic secretion of various digestive enzymes to reduce IR-induced intestinal
damage. However, the effects of pasireotide on IR-induced damage to the hematopoietic system have
not been well characterized and thus, were examined in the present study because BM failure is the
primary life‐threatening injuries after exposure to a moderate dose of IR. Specifically, we exposed CD2F1
mice to 6.0 Gy TBI (1.14Gy/min) and administered vehicle or pasireotide (1.0 mg/kg) twice per day by s.c
injection starting at 24 h after TBI for 10 days. The effects of pasireotide on TBI-induced alterations in the
hematopoietic system were examined day 15 and day 30 after TBI. Pasireotide treatment ameliorated the
reduction of RBCs induced by TBI but not that of WBCs and platelets in peripheral blood at day 15 post IR.
Furthermore, the recovery of peripheral blood neutrophils and lymphocytes in irradiated mice was greatly
accelerated upon pasireotide treatment at day 30 after irradiation compared to vehicle treated group. As
expected, TBI dramatically reduced the percentages and numbers of hematopoietic stem cells (HSCs) and
suppressed the clonogenic function of hematopoietic progenitor cells (HPCs) in the bone marrow at both
day 15 and 30 post IR. Pasireotide administration significantly attenuated the reduction of bone marrow
HSCs induced by TBI and improved HPC function revealed by colony forming cell (CFC) assays. These
findings suggest that pasireotide may reduce TBI-induced lethality in mice not only by inhibiting IR-
induced intestinal damage but also in part via attenuating IR-induced hematopoietic injury.
(PS2-80) BIO 300 (genistein oral nanosuspension) protects normal lung tissue and radiosensitizes tumor
1
tissue in a mouse xenograft model of non-small cell lung cancer (NSCLC). Stephen L. Brown ; Michael D.
2
2
2
1
Kaytor ; Karen Lapanowski ; Debra McFall ; John L. Zenk ; Ronald J. Zenk ; John C. Dykstra ; and Benjamin
1
2
1
Movsas, Henry Ford Health System, Detroit, MI and Humanetics Corporation, Minneapolis, MN
1
2
Lung cancer affects a quarter million people in the US annually, accounting for more cancer-
related deaths than any other cancer. Radiation-induced damage to normal lung tissue (pneumonitis and
fibrosis) during radiotherapy remains a significant side effect that could alter the course of therapy and/or
the outcome. The aim of the studies was to evaluate BIO 300 for efficacy in; 1) protecting normal lung
tissue from radiation-induced damage and 2) radiosensitizing tumor tissue. We also evaluated the safety
180 | P a g e
